Project 4: Post-Exposure Biomarkers and Remediation of Radionuclide Contaminants

项目4：暴露后生物标志物和放射性核素污染物的修复

• 批准号: 10327399
• 负责人: Rebecca J Abergel
• 金额: $ 37.45万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-10 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10327399
• 关键词: Acids; Actinoid Series Elements; Address; Adolescent; Animal Model; Animals; Area; Biochemistry; Biocompatible Materials; Biological; Biological Markers; Biology; Cardiovascular system; Cell physiology; Chelating Agents; Chemicals; Chemistry; Childhood; Complex; Data; Data Set; Deposition; Development; Devices; Dose; Elements; Environment; Environmental Pollution; Environmental Risk Factor; Evaluation; Event; Excision; Exposure to; Female; Foundations; Gene Expression; Gene Expression Alteration; Genes; Genetic; Health; Heavy Metals; Inhalation; Injections; Investigation; Ions; Knowledge; Laboratories; Ligands; Literature; Lung; Medical; Meta-Analysis; Metals; Modeling; Molecular; Mus; Nuclear; Nuclear Radiology; Nuclear Reactor Accidents; Particulate; Plutonium; Population; Property; Radiation; Radiation Protection; Radiation Toxicity; Radiation induced damage; Radioactive; Radioisotopes; Radiology Specialty; Regulation; Research; Research Priority; Risk; Rodent Model; Sampling; Sex Differences; Signal Pathway; System; Terrorism; Therapeutic; Time; Toxic effect; Toxicology; Treatment Efficacy; Treatment Protocols; Work; base; biomarker discovery; design; dosimetry; drug development; efficacy research; epidemiologic data; experimental study; exposed human population; functional genomics; improved; in vivo; interest; juvenile animal; male; mass casualty; mature animal; member; metal chelator; model development; nanoscale; novel therapeutics; particle; prevent; programs; remediation; respiratory; sample archive; sex; sex determination; specific biomarkers; tomography; tool; transcriptome; uptake

PROJECT 4: ABSTRACT In the last several years, a sense of urgency and a renewed interest in the study of radionuclide chemistry and biology have emerged, as threats of nuclear terrorism have become more plausible, as investigational medical tools have sought the radioactive properties of radionuclides, and as the risk of environmental contamination and human exposure to radioisotopes consequently increased. In this project, we will pursue the analysis of radionuclide distribution beyond the MACRO into the MESO, MICRO and NANO scales, in order to improve dosimetry modeling and biokinetics analyses, in line with biological endpoints, thereby enabling meaningful countermeasure development in the context of internal emitter exposures. The radiation damage and health risk presented by internalized radionuclides can be mitigated by the use of mitigators, such as decorporation agents, that reduce internal contamination. However, most effective agents enhance the elimination of only a limited range of radionuclides, and some are formulated in ways that would make administration in mass casualty situations challenging. Therefore, the development of improved decorporation therapies and better delivery systems for chelators is a research priority in the area of radiological and nuclear threat countermeasures. This project specifically addresses the urgent need to develop and implement an improved therapy for radioisotope contamination of a large population. It will establish biokinetic profiles in adult and juvenile animal models, enable the discovery of biomarkers of exposure, and extend the indication of a new therapeutic decorporation agent to selected radioisotopes in the form of inhaled particulates, by demonstrating the post-exposure potency of this product at preventing long-term lung deposition and subsequent damage. In addition, by correlating different biomarkers of radiation toxicity to countermeasure’s efficacy, this research will provide the foundational data needed to determine the need for, and course and endpoint of treatment.

项目四：摘要